Stem cells and brain repair

Group leader : P. Durbec

Our team seeks to understand the repair process in the adult brain and more specifically the regeneration of the myelin sheath.

FOR BEGINNERS

Demyelination in the corpus callosum of an adult mouse brain.

Myelin is a sheath that surrounds and insulates the nerve, and improves signal transmission. When myelin is damaged or abnormal, due to genetic abnormalities, trauma or neurodegenerative diseases such as multiple sclerosis, neurological disorders occur resulting in severe disability.

The nervous system is capable, to a certain extent, to regenerate the myelin sheath, but this self-repair process is incomplete and insufficient. This regeneration is possible thanks to the presence in the brain of stem cells and progenitor cells that can replace oligodendrocytes the myelin forming cell. It is therefore important to understand all the mechanisms involved in the process of myelin repair in order to develop new therapeutic strategies.

Oligodendrocyte progenitors migrating in culture.

Our research aims to better understand the biology of adult progenitor and stem cells involved in remyelination. Our goal is to decipher the cellular and molecular mechanisms controlling the mobilization of these cells. We are trying to determine which cells are involved in the repair process. How these cells migrate to the lesion site? What are the factors that control their differentiation into oligodendrocytes in physiological and pathological conditions? We are looking for factors that can influence or control these events when administered to the animal. We use the mouse as a model organism and combine techniques of cell biology, molecular imaging and neurosurgery to answer these questions.

FOR SPECIALISTS

Oligodendrocyte (green) and neurons (red) in co-culture.

The team focuses on the process of post-lesional plasticity following demyelination in the adult brain. In some patients affected by multiple sclerosis (MS) spontaneous remyelination can occur. Although insufficient to counter the damages caused by the repetitive attacks, this spontaneous regenerative process represent great therapeutic hopes. Studies led on rodent have identified two distinct sources of cells involved in remyelination: the oligodendrocyte progenitors (OPCs) found throughout the brain parenchyma and neural progenitor derived from the sub-ventricular zone (SVZ) were adult neural stem cells reside. Our objectives are to uncover the cellular and molecular mechanisms controlling this process in order to increase our fundamental knowledge on brain regeneration and to promote the myelin repair.

Oligodendrocyte progenitor in culture.

In our previous work, we showed that the proliferation, migration and differentiation of the OPCs and neural progenitors of the SVZ can be controlled to improve the process of cellular replacement. We identified factors that control the migration of the SVZ-derived progenitors and OPCs toward the demyelination lesions. We have shown that certain signals expressed in the lesion specifically regulate cell motility and detachment, as others are chemo-attractants.

More recently, we compared the gene expression of SVZ cells from healthy adult mice to mice with an experimental model of MS. We have identified factors whom expression is specifically regulated during the mobilization process after demyelination. We are currently focusing our attention on factors that promote angiogenesis and those that regulate the dialogue with the environment and the extracellular matrix.

Pascale Durbec

Béatrice Brousse

Myriam Cayre

Researcher

Myriam Cayre, CNRS research director, is particularly invested in the characterization of mouse models of multiple sclerosis used in the team (model of focal demyelination of the corpus callosum in the lysolecithin model of intoxication and cuprizone model of experimental autoimmune encephalomyelitis). The effort is focused on identifying the cellular and molecular processes controlling the mobilization of endogenous progenitor cells in the repair process.

Marie Falque

Julie Le Priellec

Karine Magalon

Technical staff

Karine Magalon, Research Engineer, joined the team in 2005.She provides expertise is in Biochemistry, Cell Biology and Cell Imaging. She develops models for the team of organotypic and primary cultures. She is particularly involved in the characterization of factors that promote oligodendrocyte maturation and myelination.